The overall aim of this proposal is to support the continuing development of the applicant as a scientist in the field of drug abuse treatment. The applicant's program of research is driven by two main themes: 1) That pharmacotherapies may be developed by considering the heterogeneity of drug addicted samples, and by targeting interventions to specific subgroups; and 2) That the Medications Development effort for cocaine abuse is in need of improved methods for early Phase II trials in which preliminary indications of efficacy are sought. During the proposed K02, the applicant will direct three main projects 1) A placebo-controlled trial of sertraline in methadone patients with depressive disorders and illicit drug use (R01 DA08950); 2) A placebo-controlled trial of desipramine for cocaine abusers with depressive disorders (P50 DA09236, Project 3); and 3) A series of early Phase II pilot trials for cocaine abuse candidate medications, employing a new placebo-controlled, multiple- baselines design, and incorporating human laboratory measures (R01 DA09582). The applicant will consult on epidemiologic and treatment studies of colleagues and will mentor junior collaborators on related treatment studies. The applicant will continue to pursue a training plan focused on methodology and statistics of clinical trials. Finally, the applicant will contribute to a variety of educational activities at the Medical Center, and will assume a leadership role in mentoring young clinical investigators and in the development of clinical research within the Division on Substance Abuse.